A novel hamster separation model of depression is under development for analysis of central neurochemical changes during a behavioral state of separation which may be analogous to human depression. Separated male hamsters show increased body weight, decreased exploratory behaviors, and reduced social interactions. Analysis of the time course of development of the syndrome found that a minimum of one week of separation was required. The syndrome was completely reversed by re-pairing with the original female partner. The syndrome was only partially reversed by re-pairing with a new female partner, or with a male partner. Chronic treatment with a monoamine oxidase inhibitor, tranylcypromine, was found to completely reverse the syndrome beginning at fourteen days of treatment. Receptor binding assays revealed a significant decrease in number of binding sites for 3H-amphetamine in the brainstem of separated male hamsters, as compared to paired male hamsters, suggesting that the observed change in body weight during the separation period may reflect a change in central regulation of feeding or glucose utilization.